Hematology

Question 1

Hairy Cell Leukemia— Definition, Pathogenesis, Lab Diagnosis, Clinical Features.

Answer 1

It is an uncommon B-cell neoplasm composed of neoplastic B-cells with hair-like cytoplasmic projections best seen under Phase Contrast Microscope.
M/c in middle aged men. M:F= 5:1

Pathogenesis:
BRAFV600E mutation (gain of function mutation in BRAF) — increased signalling through MAPK pathway— uncontrolled cell growth

Lab Diagnosis
1. Peripheral Smear
- RBC: Normocytic normochromic anemia
- WBC: TLC is decreased. HAIRY CELLS are seen
- Platelets: Thrbocytopenia
2. Peripheral Blood:
- Low Hb
3. Bone Marrow Aspirate shows dry tap.
Bone marrow biopsy: Honeycomb/Fried egg appearance
4. Special Stain: TRAP+

IHC markers: CD103, CD25, CD11c, Annexin A1
Clinical Features:
1. Massive splenomegaly (beefy red spleen due to red pulp involvement)
2. Pancytopenia
3. Increases risk of atypical mycobacterial infections

Question 2

Differentiate between Hodgkin and Non Hodgkin Lymphoma.

Answer 2

1. Usually single group of axial lymph nodes involved in HL while multiple peripheral LN are involved in NHL
2. HL spreads in contiguous manner while NHL has a non-contiguous and unpredictable spread
3. HL does not involve Waldeyer ring/Mesenteric LN while NHL frequently involves them
4. Extranodal presentation is uncommon in HL but common in NHL
5. Reed Sternberg cells are seen in HL but not in NHL

Question 3

What are the types of Hodgkin Lymphoma.

How will you differentiate between Classical and Nonclassical type?

Answer 3

Types of HL

1. Classical
   a) nodular sclerosis CHL
   b) Mixed Cellularity
   c) Lymphocyte Rich
   d) Lymphocyte Depleted
2. Non-classical- Nodular Lymphocyte Predominant HL (NLPHL)

Classical HL is CD15+, CD30+
NLPHL is CD20+, CD45+, EMA+, BCL-6+

Question 4

Polycythemia Vera— Definition, Pathogenesis, Diagnostic criteria, Lab diagnosis, Clinical features, Treatment.

Answer 4

PCV is a Myeloproliferative neoplasm with increased marrow production of erythrocytes, granulocytes and megakarocytes but clinical symptoms are mainly due to increase in red cell count.

Pathogenesis: JAK2 V617F mutation. JAK2 is a tyrosine kinase which lies downstream of many growth factor signalling pathways, including erythropoietin receptors. Mutation leads to constitutive activation of JAK2— erythropoietin independent proliferation.

• Increase RBC Count– increased blood viscosity and slugging
• Thrombocytosis
• Abnormal platelet function

WHO Criteria 
-Major: 
Hb >16.5 g/dL for men and >16g/dL in women 
Presence of JAK2V617F mutation
Panmyelosis 
- Minor: Low EPO level

Lab diagnosis:

1) CBC: Hb high, Platelet count high
2) Peripheral smear: Normocytic normochromic RBC, Leukocytosis, Basophilia, Giant platelets, Increase LAP Score
3) BM aspirate: Hypercellular, increase in Erythroid progenitors + granulocytic and megakaryocytic precursors
4) Increased reticulum fibres

Clinical:

1. Thrombosis and hemorrhagic symptoms: Minor bleeds (epistaxis) and major bleeds
2. Hepatosplemomegaly
3. Cyanosis, headache, hypertension, neuro abnormalities
4. Intense pruritus (itching)

Treatment: Phlebotomy

Question 5

Myelofibrosis— Definition, Pathogenesis, clinical features, lab diagnosis.

Answer 5

It’s a myeloproliferative neoplasm (MPN) characterised by obliterative marrow fibrosis.

Pathogenesis: Growth factor independence due to constitute activation of receptor tyrosine kinase JAK2. Other mutations may be CALR, MPL

Clinical features: Progressive anemia, Splenomegaly (extramedullary hematopoeisis), Hyperurecemia and gout (due to increased cel, turnover). Non specific: Weight loss, night sweats, fatigue.

Lab diagnosis:
CBC: Hb is low, PC is low
PSE: Teardrop cells (Dacrocytes), Leukoerythroblastic blood picture, Nucleated RBC precursors and Immature WBC precursors in blood
BM biopsy: essential for diagnosis as aspirate gives Dry Tap.
- Initially hyper-cellular, later fibrotic and hypocellular
- Atypical megakaryocyted (Cloud like nuclei)
- Increased reticulin fibres
- Osteosclerosis

Question 6

Disorders with longitudinal grooves on H&E microscopy.

Answer 6

1. Langerhans cell histiocytosis(Coffee bean appearance)
2. Papillary Ca of thyroid
3. Brenner’s tumor
4. Chindroblastoma
5. Granulosa cell tumor

Question 7

BRAF mutations are seen in which cancers.

Answer 7

1. Langerhans Cell Histiocytosis
2. Papillary Carcinoma of Thyroid
3. Melanoma
4. Colon cancer
5. Hairy Cell Leukemia

Question 8

Diagnosis of Sickle Cell Anemia.

Answer 8

1) Peripheral Blood - Hb low, Hematocrit low, Reticulocytosis

2) Peripheral Smear
- Microcytic hypochromic anemia
- Sickle cells
- Target cells

3) Bone marrow aspiration
- Hypercellular
- Erythroid hyperplasia
- Myelopoeisis and megakaryopoeisis: normal

4) Confirmatory Tests
- Sickling Test
- Solubility Test for HbS
- Hb electrophoresis
- HPLC
- HbF estimation